A 71-year-old woman with multiple myeloma developed large, nonhemorrhagic bullae on the skin of one arm during the course of septicemia due to Escherichia coli, serotype 04. Atraumatic aspiration of the skin lesions revealed E coli of the same serotype. Other causes of subepidermal bullae could be eliminated on clinical or laboratory grounds or both. Clear bullae may be another, albeit rare, manifestation of systemic bacterial infection.